Fungicides are compounds, of natural or synthetic origin, which act to protect and/or cure plants against damage caused by agriculturally relevant fungi. Generally, no single fungicide is useful in all situations. Consequently, research is ongoing to produce fungicides that may have better performance, are easier to use, and cost less.
The present disclosure relates to macrocyclic picolinamides and their use as fungicides. The compounds of the present disclosure may offer protection against ascomycetes, basidiomycetes, deuteromycetes and oomycetes.
One embodiment of the present disclosure may include compounds of Formula I:

X is H or C(O)R5;
Y is H, C(O)R5, or Q;
Q is

R1 is H, alkyl, alkenyl, aryl, —C(O)R4, each substituted with 0, 1 or multiple R4;
R2 is H, alkyl, alkenyl, aryl, —C(O)R4, each substituted with 0, 1 or multiple R4;
R3 is H, —C(O)R6 or —CH2OC(O)R6;
R4 is alkyl, alkenyl, halo, haloalkyl, alkoxy, or aryl;
R5 is alkyl, alkoxy, benzyl, benzyloxy, each substituted with 0, 1, or multiple R7, wherein each R7 may be substituted with 0, 1, or multiple R4;
R6 is alkyl or alkoxy, each substituted with 0, 1, or multiple R4;
R7 is alkyl, alkenyl, halo, haloalkyl, alkoxy, aryl, heteroaryl, carbocyclic, heterocyclic, —Si(R4)3, —C(O)R4, —S(O)nR4, each substituted with 0, 1, or multiple R4;
and with the proviso that when R1 and R2 are H then X and Y are C(O)R5 and R5 is tert-butoxy.
Another embodiment of the present disclosure may include a fungicidal composition for the control or prevention of fungal attack comprising the compounds described above and a phytologically acceptable carrier material.
Yet another embodiment of the present disclosure may include a method for the control or prevention of fungal attack on a plant, the method including the steps of applying a fungicidally effective amount of one or more of the compounds described above to at least one of the fungus, the plant, an area adjacent to the plant, and the seed adapted to produce the plant.
The term “alkyl” refers to a branched or unbranched carbon chain, including methyl, ethyl, propyl, butyl, isopropyl, isobutyl, tertiary butyl, pentyl, hexyl, cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl and the like.
The term “alkenyl” refers to a branched or unbranched carbon chain containing one or more double bonds including ethenyl, propenyl, butenyl, isopropenyl, isobutenyl, cyclopentenyl, cyclohexenyl, and the like.
The term “alkynyl” refers to a branched or unbranched carbon chain containing one or more triple bonds including propynyl, butyryl and the like.
The term “aryl” refers to any aromatic, mono- or bi-cyclic, containing 0 heteroatoms.
The term “heterocyclyl” refers to any aromatic or non-aromatic ring, mono- or bi-cyclic, containing one or more heteroatoms
The term “cycloalkyl” refers to any monocyclic or polycyclic, saturated substituent consisting of carbon and hydrogen, for example, cyclopropyl, cyclobutyl, cyclopentyl, norbornyl, bicyclo[2.2.2]octyl, and decahydronaphthyl.
The term “cycloalkenyl” refers to any monocyclic or polycyclic, unsaturated (at least one carbon-carbon double bond) substituent consisting of carbon and hydrogen, for example, cyclobutenyl, cyclopentenyl, cyclohexenyl, norbornenyl, bicyclo[2.2.2]octenyl, tetrahydronaphthyl, hexahydronaphthyl, and octahydronaphthyl.
The term “alkoxy” refers to an —OR substituent.
The term “alkoxycarbonyl” refers to a —C(O)—OR substituent.
The term “alkylcarbonyl” refers to a —C(O)—R substituent.
The term “alkylsulfonyl” refers to an —SO2—R substituent.
The term “haloalkylsulfonyl” refers to an —SO2—R substituent where R is fully or partially substituted with Cl, F, I, or Br or any combination thereof.
The term “alkylthio” refers to an —S—R substituent.
The term “haloalkylthio” refers to an alkylthio, which is substituted with Cl, F, I, or Br or any combination thereof.
The term “alkylaminocarbonyl” refers to a —C(O)—N(H)—R substituent.
The term “dialkylaminocarbonyl” refers to a —C(O)—NR2 substituent.
The term “alkylcycloalkylamino” refers to a cycloalkylamino substituent that is substituted with an alkyl group.
The term “trialkylsilyl” refers to —SiR3.
The term “cyano” refers to a —C≡N substituent.
The term “hydroxyl” refers to an —OH substituent.
The term “amino” refers to a —NH2 substituent.
The term “alkylamino” refers to a —N(H)—R substituent.
The term “dialkylamino” refers to a —NR2 substituent.
The term “alkoxyalkoxy” refers to —O(CH2)nO(CH2)n where n is an integer selected from the list 1, 2, 3, 4, 5, or 6.
The term “alkoxyalkyl” refers to an alkoxy substitution on an alkyl.
The term “haloalkoxyalkyl” refers to an alkoxy substitution on an alkyl which may be partially substituted with halogen atoms.
The term “hydroxyalkyl” refers to an alkyl which is substituted with a hydroxyl group.
The term “haloalkoxy” refers to an —OR—X substituent, wherein X is Cl, F, Br, or I, or any combination thereof.
The term “haloalkyl” refers to an alkyl, which is substituted with Cl, F, I, or Br or any combination thereof.
The term “haloalkenyl” refers to an alkenyl, which is substituted with Cl, F, I, or Br or any combination thereof.
The term “haloalkynyl” refers to an alkynyl which is substituted with Cl, F, I, or Br or any combination thereof.
The term “halogen” or “halo” refers to one or more halogen atoms, defined as F, Cl, Br, and I.
The term “hydroxycarbonyl” refers to a —C(O)—OH substituent.
The term “nitro” refers to a —NO2 substituent.
The term “optionally substituted with” a substituent means containing 0, 1, or more of that substituent.
Unless specifically noted or clearly implied otherwise the term “about” refers to a range of values of plus or minus 10 percent, e.g. about 1 refers to the range 0.9 to 1.1.
Throughout the disclosure, reference to the compounds of Formula I is read as also including diastereomers, enantiomers, and mixtures thereof. In another embodiment, Formula (I) is read as also including salts or hydrates thereof. Exemplary salts include, but are not limited to: hydrochloride, hydrobromide, and hydroiodide.
It is also understood by those skilled in the art that additional substitution is allowable, unless otherwise noted, as long as the rules of chemical bonding and strain energy are satisfied and the product still exhibits fungicidal activity.
Another embodiment of the present disclosure is a use of a compound of Formula I, for protection of a plant against attack by a phytopathogenic organism or the treatment of a plant infested by a phytopathogenic organism, comprising the application of a compound of Formula I, or a composition comprising the compound to soil, a plant, a part of a plant, foliage, roots, and/or seeds.
Additionally, another embodiment of the present disclosure is a composition useful for protecting a plant against attack by a phytopathogenic organism and/or treatment of a plant infested by a phytopathogenic organism comprising a compound of Formula I and a phytologically acceptable carrier material.
In one embodiment, a compound of Formula (I) is provided:

wherein:
X is H or C(O)R5;
Y is H, C(O)R5, or Q;
Q is

R1 is H, alkyl, alkenyl, aryl, —C(O)R4, each optionally substituted with one or more R4;
R2 is H, alkyl, alkenyl, aryl —C(O)R4, each optionally substituted with one or more R4;
R3 is H, —C(O)R6 or —CH2OC(O)R6;
R4 is alkyl, alkenyl, halo, haloalkyl, alkoxy, or aryl;
R5 is alkyl, alkoxy, benzyl, benzyloxy, each optionally substituted with one or more R7, wherein each R7 may be optionally substituted with one or more R4;
R6 is alkyl or alkoxy, each optionally substituted with one or more R4;
R7 is alkyl, alkenyl, halo, haloalkyl, alkoxy, aryl, heteroaryl, carbocyclic, heterocyclic, and —Si(R4)3, —C(O)R4, —S(O)nR4, each optionally substituted with one or more R4;
with the proviso that when R1 and R2 are H, X and Y are C(O)R5 and R5 is tert-butoxy.
In one more particular embodiment, X and Y are independently chosen from H or C(O)R5. In an even more particular embodiment, X and Y are C(O)R5 and R5 is independently chosen from alkyl, alkoxy, benzyl, or benzyloxy, each optionally substituted with one or more R7, wherein each R7 may be optionally substituted with one or more R4. In a still more particular embodiment, R1 and R2 are independently chosen from H, alkyl, alkenyl, aryl, or —C(O)R4, each optionally substituted with one or more R4.
In one embodiment, R5 is alkoxy and R1 and R2 are H.
In one embodiment, R5 is tert-butoxy. In one embodiment, X and Y are hydrogen. In a more particular embodiment, R1 and R2 are independently chosen from H, alkyl, alkenyl, aryl, or —C(O)R4, each optionally substituted with one or more R4.
In one embodiment, R1 and R2 are independently alkyl, alkenyl, aryl, or —C(O)R4, each optionally substituted with one or more R4.
In one embodiment, R1 and R2 are independently alkyl or aryl, each optionally substituted with one or more R4.
In one embodiment, the amine is protonated to give an ammonium salt of a mineral acid independently chosen from hydrogen chloride, hydrogen bromide, or hydrogen iodide. In a more particular embodiment, the ammonium salt is the ammonium hydrochloride.
In one embodiment, X is H and Y is Q.
In one embodiment, R1 and R2 are independently chosen from H, alkyl, alkenyl, aryl, or —C(O)R4, each optionally substituted with one or more R4.
In one embodiment, R1 and R2 are independently alkyl, alkenyl, aryl, or —C(O)R4, each optionally substituted one or more R4.
In one embodiment, R1 and R2 are independently alkyl or aryl, each optionally substituted with one or more R4.
In one embodiment, R3 is H, —C(O)R6 or —CH2C(O)R6. In a more particular embodiment, R3 is H. In another more particular embodiment, R3 is C(O)R6. In a further particular embodiment, R6 is alkyl or alkoxy, each optionally substituted with one or more R4. In another further particular embodiment, R6 is alkyl, optionally substituted with one or more R4. In still another further particular embodiment, R6 is —CH3 or —CH2CH2—R4 and R4 is OCH3. In another more particular embodiment, R3 is —CH2OC(O)R6. In a further particular embodiment, R6 is alkyl or alkoxy, each optionally substituted with one or more R4. In another further particular embodiment, R6 is alkyl, each optionally substituted with one or more R4. In still another more particular embodiment, R6 is —CH3 or —CH(CH3)2.
In one embodiment, a composition is provided for the control of a fungal or fugal like pathogen. In one embodiment, the composition includes the compound of Formula I as defined by any of the above embodiments and a phytologically acceptable carrier material. The combination of Formula I and the carrier is useful for the control of fungal and fungal like pathogens. In a more particular embodiment, the fungal or fungal like pathogen is selected from the group consisting of: Mycosphaerella graminicola(Septoria tritici), Puccinia triticina, Puccinia striiformis, Venturia inaequalis, Uncinula necator, Rhynchosporium secalis, Magnaporthe grisea, Phakopsora pachyrhizi, Leptosphaeria nodorum, Blumeria graminis f. sp. tritici, Blumeria graminis f. sp. hordei, Erysiphe cichoracearum, Glomerella lagenarium, Cercospora beticola, and Alternaria solani. In a further particular embodiment, the fungal pathogen or fungal like pathogen is selected from the group consisting of: Septoria tritici and Puccinia triticina. 
In one embodiment, a method for the control and prevention of plant disease is provided. The method includes applying a fungicidally effective amount of at least one of the compounds of Formula I as defined by any of the above embodiments to at least one surface selected from the group consisting of: at least one surface of a plant, an area adjacent to a plant, soil in contact with a plant, soil adjacent to a plant, seeds, and equipment for use in agriculture. In a more particular embodiment, the fungicidally effective amount Formula I is applied to a surface in the range of about 0.01 g/m2 to about 0.45 g/m2 of Formula I.